198 - Saliva miRNA biomarkers of neonatal opioid withdrawal syndrome
Sunday, April 30, 2023
3:30 PM – 6:00 PM ET
Poster Number: 198 Publication Number: 198.333
Rhea E. Sullivan, Penn State College of Medicine, Hershey, PA, United States; Steven Hicks, Pennsylvania State University College of Medicine, Hershey, PA, United States; Kim K. Doheny, Penn State Health Children's Hospital and Penn State College of Medicine, Hershey, PA, United States; Christiana Oji-Mmuo, Penn State Children's Hospital, Hershey, PA, United States
MD/PhD student Penn State College of Medicine Hershey, Pennsylvania, United States
Background: Clinical decisions for the initiation of morphine therapy in neonatal opioid withdrawal syndrome (NOWS) rely on assessment with subjective symptom scales. Development of biologic markers for NOWS could aid objective quantification of withdrawal severity, risk stratification for earlier NOWS admission, and selection of optimum morphine dose. Objective: The objective of this study was to determine if miRNAs that regulate opioid signaling and brain development (miR-146a, let-7a, miR-23b, miR-192) are perturbed in NOWS. Design/Methods: This case control study involved 13 infants with NOWS and 13 age/sex-matched controls without maternal substance use. Exclusion criteria were: gestational age < 37 weeks, mechanical ventilation, neonatal infection, or maternal polysubstance abuse. Saliva samples were collected from all infants within seven days of delivery (before the first treatment dose of morphine). A second saliva sample was collected from NOWS participants at discharge (following morphine treatment). RNA was extracted from all saliva samples, and polymerase chain reactions were used to quantify miR-146a, let-7a, miR-23b, and miR-192 levels. A Mann-Whitney U-test was used to compare miRNA levels between: 1) NOWS and control infants at enrollment, 2) NOWS infants who required morphine treatment and NOWS infants who did not; and 3) NOWS infants at discharge and control infants. Results: Participants were 23% female, and were born at 38 weeks gestation, on average. Also, 53.8% of participants required morphine treatment. Saliva levels of miR-146a and miR-192 were decreased in the saliva of infants with NOWS compared to healthy infants (miR-146a, p = 0.0001, Cohen’s d = 0.74; miR-192, p = 0.0003, d = 0.756; let-7a, p = 0.093, d = 0.321, miR-23b, p = 0.113, d = 0.295. No miRNAs differed between NOWS infants who required morphine therapy, and NOWS infants who did not (miR-146a, p = 0.113; miR-192, p = 0.052; let-7a, p = 0.090; miR-23b, p = 0.223). After completion of morphine therapy, levels of miR-146a remained decreased in infants with NOWS (p = 0.0067, d = 0.722), whereas levels of miR-192 no longer differed from healthy infants (p = 0.106, d = 0.389).
Conclusion(s): These results suggest that levels of opioid-related miRNAs (i.e., miR-192) are perturbed in the saliva of infants with NOWS, but may recover toward levels observed in healthy peers after successful symptom control with morphine treatment. Confirmation in a larger external cohort is necessary. Further studies could explore whether miR-192 expression could predict the optimum morphine dose necessary for NOWS symptom control.
